Study Guide for the 2 midterm exam

Study Guide for the 2 nd midterm exam Anth/Biol 5221, 31 October 2011
Mutation, drift, and population size change
1. How are the sizes and shapes of gene genealogies affected when the population size N
increases or decreases? (Assume selective neutrality.)
2. How are the relationships of , S and 2N affected when the population size has recently
increased or decreased?
Site frequency spectrum and mismatch distribution
3. Be able to calculate them from data (for small, simple data sets), and understand how they
relate to the sizes and shapes of gene genealogies.
4. How do they respond to changes of population size (as in #2)?
Neutral theory
5. What is the rate of molecular evolution ()?
6. Why does = μ at a neutral site (even when selection strongly affects closely linked sites)?
7. What is the central empirical claim of the neutral theory?
8. How is a “molecular clock” calibrated (retrospectively)?
Selection in a large population
Each of the questions in this section could be framed in different ways. For example, we might
give you symbols for the three genotypic fitnesses and the two allele frequencies, and ask for an
answer in terms of those symbols. Or we might give you numbers and ask for numbers.
9. Assuming fixed, constant fitnesses for the three genotypes at a biallelic diploid locus (W11,
W12, W22), what is the mean fitness of the population?
10. What are the marginal fitnesses of the two alleles?
11. What is next generation’s expected allele frequency (p’ or q’) as a function of these
quantities?
12. How can an observed rate of allele-frequency change be used to estimate the relative
fitnesses of two alleles (for example, s, if we know the value of h)? This was the subject of some
homework problems.
Mutation-selection balance and the genetic load
13. In a large population (i.e., ignoring drift), what is the equilibrium frequency of deleterious
recessive alleles (h = 0) at a locus where the mutation rate to such alleles is μ per generation and
the selective disadvantage of the mutant homozygotes is s?
14. What is the approximate equilibrium frequency of partially recessive mutations (0 < h < 0.5)
under otherwise identical circumstances?

15. What is the mean fitness of a large population where a locus is subject to deleterious
mutations of effect-size s, dominance h, and these mutations occur at rate μ per gene copy per
generation? Why do s and h not appear in the answer?
Interactions of mutation, drift and selection
16. What is the probability of fixation for a newly arisen neutral mutation? Probability of loss?
17. What is the approximate fixation probability for a newly arisen mutation that is favored by a
selection coefficient of s (relative fitness 1 + s) in the homozygous state, and s/2 in the
heterozygous state? Does the population size N affect our answer? If so, how?
18. What is the expected rate at which adaptive mutations will fix within a species, given a
certain population size (N), selective advantage (s), and genome-wide rate of mutation (U) to
alleles with advantages of about that size?
19. Why are most of our deleterious mutations (the ones segregating at appreciable frequencies)
at least partly recessive?
20. Under what conditions will a deleterious (harmful) mutation have nearly as good a chance of
fixing as a neutral mutation?
21. Do we expect more adaptive evolution in large or small populations? Explain.
22. Do we expect to find more or fewer harmful mutations segregating in a selfing plant species
(for example, rice) than in a predominantly outbreeding relative? Explain.
Linkage disequilibrium between two loci
23. How do we describe the population frequencies of multi-locus genotypes, in the simplest
case involving a pair of loci each with two alleles? (For example, suppose one locus has alleles A
and a, and the other locus has alleles B and b.)
24. What’s the relationship between the allele frequencies at each locus, and the gamete or
haplotype frequencies (that is, the frequencies of the haploid pairings AB, Ab, aB and ab)?
25. If we gave you the frequencies of these four gamete types, you should be able to give us the
allele frequencies and D (the coefficient of linkage disequilibrium). Or the other way around.
26. Locus B has two alleles: B1 (with frequency p1), and B2 (with frequency p2 = 1−p1). A new
mutation arises at a linked locus, C. What is the probability that this mutant chromosome carries
allele B1?
Please note that almost every one of these questions is very easy to answer if you understand the
terminology and a few elementary principles of probability – the ideas we’ve been stressing from
day one of this course. There’s very little to memorize. Be confident, you can reason it out!